Effects of Oral Retinoid (Vitamin a and Etretinate) Therapy on Photocarcinogenesis in Hairless Mice

Kelly, Graham; Meikle, W.; Sheil, A. G. R.

doi:10.1111/j.1751-1097.1989.tb04150.x

Cited by 9 publications

(4 citation statements)

References 9 publications

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“…These variable effects of RA may also be due to differences in the background strain of the hairless gene mutation, as different mouse strains have different susceptibility to cSCC and different levels of endogenous retinoids [122,123]. Oral retinol or the second-generation aromatic retinoid etretinate at two high doses also did not alter photocarcinogenesis in hairless mice [124]. These studies suggest a complex relationship between UVB, cSCC development, and RA signaling.…”

Section: Retinoids and Cutaneous Squamous Cell Carcinoma (Cscc)mentioning

confidence: 87%

Retinoids in Cutaneous Squamous Cell Carcinoma

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Akuailou

2021

Nutrients

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Animal studies as early as the 1920s suggested that vitamin A deficiency leads to squamous cell metaplasia in numerous epithelial tissues including the skin. However, humans usually die from vitamin A deficiency before cancers have time to develop. A recent long-term cohort study found that high dietary vitamin A reduced the risk of cutaneous squamous cell carcinoma (cSCC). cSCC is a form of nonmelanoma skin cancer that primarily occurs from excess exposure to ultraviolet light B (UVB). These cancers are expensive to treat and can lead to metastasis and death. Oral synthetic retinoids prevent the reoccurrence of cSCC, but side effects limit their use in chemoprevention. Several proteins involved in vitamin A metabolism and signaling are altered in cSCC, which may lead to retinoid resistance. The expression of vitamin A metabolism proteins may also have prognostic value. This article reviews what is known about natural and synthetic retinoids and their metabolism in cSCC.

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Section: Retinoids and Cutaneous Squamous Cell Carcinoma (Cscc)mentioning

confidence: 87%

Retinoids in Cutaneous Squamous Cell Carcinoma

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Akuailou

2021

Nutrients

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“…First, the hr/h and Oslo/Bom strains of hairless mice were more sensitive to vitamin A supplementation than was anticipated from data in the literature (22). Addition of no more than 4-6 mg of retinol per kg diet, which should correspond to a daily intake of~30 µg (100 IU) per animal (7,23), produced steady-state concentrations of vitamin A in the liver and skin that were well above the normal range (20), and 10 times this amount of supplementation elicited overt signs of hypervitaminosis A. Secondly, retinol-supplemented animals showed an increased incidence of UV-induced skin tumours compared with unsupplemented controls. This result, which was obtained with both UVB and UVAB irradiation, differs from the inability of dietary vitamin A to influence UV carcinogenesis observed in a study by Kelly et al (23).…”

Section: Discussionmentioning

confidence: 99%

Potentiating effect of dietary vitamin A on photocarcinogenesis in hairless mice

Mikkelsen¹

1998

Carcinogenesis

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Vitamin A and its derivatives (retinoids) exert modulatory effects on epithelial differentiation and are used therapeutically against skin cancers, but the role of dietary vitamin A in ultraviolet (UV)-induced carcinogenesis is far from clear. To study this process, 220 hairless mice were given diets containing low (0.3-0.6 mg/kg; A-) or high (4-6 mg/kg; Aϩ) amounts of retinol, which resulted after 2 months in an~4-fold difference in liver and skin vitamin A levels as determined by HPLC. Commencing after 1 month of diet, daily irradiations with UVB (280-320 nm) or UVAB (280-380 nm) were given to 176 of the animals for 18 weeks (cumulative doses of UVB and UVA: 26 J/cm 2 and 168 J/cm 2 , respectively). The first skin tumours, known to be squamous cell carcinomas, appeared after 35 weeks in the UVAB-irradiated Aϩ animals and 5-6 weeks later in the other groups. After one year the frequency of tumour-bearing animals was 49-63% in the Aϩ groups and 28-39 % in the A-groups (P ϭ 0.003). Two months later the corresponding figures were 66-72% and 50-53%, respectively (P ϭ 0.014). Disregarding the effect of dietary vitamin A, there was no difference in the final tumour incidence between UVB-and UVAB-irradiated animals. The epidermal vitamin A content at 72 h postirradiation was~60% lower in Aϩ animals and~10% lower in A-animals compared with the non-irradiated controls. Rather than protecting against skin cancer, a diet rich in vitamin A seems to facilitate UV carcinogenesis in hairless mice. A possible explanation is that photodecomposition of excessive vitamin A generates short-lived intermediates that may act as photosensitizers during cutaneous carcinogenesis.

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“…These differential effects could be due to either the dose of RA or differences in the background strain. Both oral retinol and etretinate also failed to alter photocarcinogenesis when given at two high doses . In humans, low doses of oral retinoids prevent the reoccurrence of carcinomas in high‐risk patients; but significant prevention by oral retinoids only occurs for a few years and relapse occurs upon stopping treatment .…”

Section: Introductionmentioning

confidence: 99%

Endogenous Retinoic Acid Required to Maintain the Epidermis Following Ultraviolet Light Exposure in SKH‐1 Hairless Mice

Gressel

Duncan

Oberyszyn

et al. 2015

Photochem & Photobiology

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Ultraviolet light B (UVB) exposure induces cutaneous squamous cell carcinoma (cSCC), one of the most prevalent human cancers. Reoccurrence of cSCC in high-risk patients is prevented by oral retinoids. But oral retinoid treatment causes significant side effects; and patients develop retinoid resistance. Exactly how retinoids prevent UVB-induced cSCC is currently not well understood. Retinoid resistance blocks mechanistic studies in the leading mouse model of cSCC, the UVB exposed SKH-1 hairless mouse. To begin to understand the role of retinoids in UVB-induced cSCC we first examined the localization pattern of key retinoid metabolism proteins by immunohistochemistry 48 hours after UVB treatment of female SKH-1 mice. We next inhibited retinoic acid (RA) synthesis immediately after UVB exposure. Acute UVB increased RA synthesis, signaling, and degradation proteins in the stratum granulosum. Some of these proteins changed their localization; while other proteins just increased in intensity. In contrast, acute UVB reduced the retinoid storage protein lectin:retinol acyltransferase (LRAT) in the epidermis. Inhibiting RA synthesis disrupted the epidermis and impaired differentiation. These data suggests that repair of the epidermis after acute UVB exposure requires endogenous RA synthesis.

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Effects of Oral Retinoid (Vitamin a and Etretinate) Therapy on Photocarcinogenesis in Hairless Mice

Cited by 9 publications

References 9 publications

Retinoids in Cutaneous Squamous Cell Carcinoma

Retinoids in Cutaneous Squamous Cell Carcinoma

Potentiating effect of dietary vitamin A on photocarcinogenesis in hairless mice

Endogenous Retinoic Acid Required to Maintain the Epidermis Following Ultraviolet Light Exposure in SKH‐1 Hairless Mice

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